The classical strategy in human vaccination based on the immunostimulation of the microorganism structural antigens has been somewhat disappointing. The number of authorized vaccines used to confer immunity in humans represents a very small percentage of all the pathogenic microorganisms known worldwide. There is not yet available any effective vaccine against fungi, protozoa or helminths. However, several findings suggest that vaccination proves to be efficacious when immunoneutralization of microbial agents associated with virulence occurs. Two of the most effective human vaccines, tetanus and diphtheria, are directed towards bacterial toxins and not to the bacteria structural epitopes. It is also worth mentioning that the vaccine against smallpox consists of a virus, not completely attenuated, since vesicles and pustules appear on the skin at the vaccination site. In previous studies, the inventors of the vaccine against dental caries have demonstrated that several pathogenic microorganisms release virulence-associated immunomodulatory proteins (1-.4). The immunoneutralization of these proteins developed a preventive action in the host, protecting it against systemic infections caused both by the fungus Candida albicans and the bacterium Streptococcus mutans (5,6). Furthermore, preventive vaccination against systemic candidiasis occurred for the first time in primates (marmosets) through immunization against the immunomodulatory protein produced by the fungus (D. Tavares, unpublished communication). Recently, it was reported that a racemase excreted by the protozoon Trypanosoma cruzi (7) preventively protects the host from the systemic infection caused by the parasite (Patent application PCT/IB00/02008, from the Pasteur Institute et al., submitted on Dec. 4, 2000).
The bacteria Streptococcus sobrinus and S. mutans have already been identified as the main etiologic agents of tooth decay in humans (8-11). The treatment of dental caries probably is the most expensive one at world level due to the disease high incidence all over (8,11). Both children and teenagers as well as adults can benefit from vaccination since it prevents pathological complications associated with cariogenicity. Actually, it is well known that Streptococci infections are responsible, in 55% of the cases, for endocarditis and are frequently detected in immunodepressed patients. Therefore, a vaccine against dental decay will reduce risk factors in patients suffering from congenital heart disease or having a heart implanted device and will have a helpful effect on other pathologies or clinical disorders associated with bacterial colonization.
The cariogenic bacteria S. sobrinus and S. mutans excrete into the culture medium proteins whose characteristics are identical to those reported in other microorganisms (1-4). These proteins have in common the following: i) they are mitogenic proteins, inducing lymphocyte polyclonal activation in the host (1-4); ii) they induce the early production of IL-10, an anti-inflammatory cytokine (12,13); iii) they are associated with the microorganism virulence once there is a direct relationship between its production and the microbe pathogenicity (4,14) and are iv) important to the survival of the microorganism in the host as the treatment of the latter with these proteins before occurring the infection enhances the parasitic loading (2,4,14). Consequently, the production of these immunomodulatory proteins seems to be an evasion mechanism used by some pathogens. The protein responsible for the immunosuppressor activity of the VIP produced by S. sobrinus was recently identified as an enolase according to a N-terminal basis and the gene that encodes it cloned, sequenced and expressed into a heterologous system in order to obtain the recombinant protein (15).